First-in-Human Dose-escalation of GSK4425689A: Safety, Tolerability, and PK in Healthy Adults
Trial overview
Number of participants with adverse events (AEs) overall and by severity
Timeframe: From Day 1 up to Day 364
Number of participants with serious adverse events (SAEs) overall and by severity
Timeframe: From Day -28 [informed consent form (ICF) signing] up to Day 364
Bioavailability (F) of SC administration
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1 hour (h)) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Terminal serum half-life (t1/2)
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Clearance (CL) of IV administration and apparent clearance (CL/F) of SC administration
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Volume of distribution (Vd) of IV administration and apparent volume of distribution (Vd/F) of SC administration
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Maximum observed serum concentration (Cmax)
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Time to reach Cmax (Tmax)
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Area under the serum concentration-time curve (AUC) from time zero up to 168 hours (AUC0-168)
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120 and 168 hours post-dose
AUC0-672
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504 and 672 hours post-dose
AUC from time zero up to the time of the last quantifiable sample (AUC0-t)
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
AUC extrapolated to infinity (AUC0-inf)
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approximately 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Dose proportionality of Cmax following IV administration
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approx. 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Dose proportionality of AUC0-t following IV administration
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approx. 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Dose proportionality of AUC0-inf following IV administration
Timeframe: From Day 1 until Day 197 [samples taken at pre-dose (within 1h) and at approx. 4, 8, 12, 24, 48, 72, 96, 120, 168, 336, 504, 672, 1344, 2016, 2688, 3360 and 4032 hours post-dose
Participation criteria
- 1. Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- 2. Participants must have a body weight between 50 and 100 kg, inclusive and body-mass index (BMI) within the range of 18.0 to 32.0 kg/m^2.
- 1. Participants with a history of malaria infection or who have previously participated in malaria vaccine trials or studies involving experimental anti-malarial monoclonals, small molecule drugs, or experimental malaria challenge are excluded. Participants who have been vaccinated against malaria with an investigational or approved vaccine (e.g., RTS,S and R21/Matrix-M) are excluded.
- 2. History of allergy to humanized monoclonal antibodies (mAbs) or constituents of the formulation.
- 1. Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent. 2. Participants must have a body weight between 50 and 100 kg, inclusive and body-mass index (BMI) within the range of 18.0 to 32.0 kg/m^2. 3. Participants must be healthy male or female participant of non-childbearing potential (PONCBP). 4. Participants must be capable of giving signed informed consent prior to any study-specific procedures, which include compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 5. Participants must demonstrate the ability to understand and comply with the study requirements, including attendance for all scheduled visits and adherence to protocol-specified procedures and restrictions. Participants must be willing to remain in close contact with study personnel and reliably record data as instructed. 6. Participants must be in good general health and have no significant ongoing medical conditions, as determined by comprehensive medical history, thorough physical examination, vital signs assessment, 12-lead ECG, and clinical laboratory evaluations (including hematology, biochemistry, and urinalysis). 7. Participants should have baseline (screening) clinical laboratory values (renal, hepatic, and hematological) within normal limits or clinically acceptable to the investigator. A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, or outside the normal reference range for the population being studied, may be included only if the investigator considers that the finding is unlikely to introduce additional risk factors for the participant and will not interfere with the study procedures or endpoints. 8. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels must be within the normal range at Screening.
- 1. Participants with a history of malaria infection or who have previously participated in malaria vaccine trials or studies involving experimental anti-malarial monoclonals, small molecule drugs, or experimental malaria challenge are excluded. Participants who have been vaccinated against malaria with an investigational or approved vaccine (e.g., RTS,S and R21/Matrix-M) are excluded. 2. History of allergy to humanized monoclonal antibodies (mAbs) or constituents of the formulation. 3. Any history of anaphylaxis or other severe allergic reactions, or food, or drug allergy that may impact participant safety in the opinion of the investigator. 4. Recent history of, or presence of a current or suspected chronic disease that may impact participant safety, or impact interpretation of clinical study results. This includes illnesses such as (but not limited to) cardiac disease, autoimmune disease, diabetes, progressive neurological disease, severe malnutrition, hepatic or renal disease, epilepsy, chronic obstructive pulmonary disease or asthma (except resolved childhood asthma, which is acceptable). Conditions that in the opinion of the investigator constitute a risk to the individual when taking the study intervention or likely to interfere with the interpretation of data. 5. Have a history of malignant neoplasm (other than localized basal or squamous cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within 5 years of Screening, regardless of whether there is evidence of local recurrence or metastases. 6. Current enrolment or participation in another clinical study. 7. Participation in another clinical study involving any investigational product within the past 90 days or within a period equivalent to 5 half-lives of the investigational drug, whichever is longer, or receipt of experimental non-malaria vaccines or mAbs within the past 12 months prior to signing the informed consent. 8. QT corrected for heart rate by Fridericia’s formula (QTcF) >450 msec. 9. Presence or history of cardiac arrhythmias or cardiac disease or a family or personal history of long-QT syndrome. 10. Average heart rate of <40 or >100 beats per minute (bpm). 11. Evidence of previous myocardial infarction or any clinically significant conduction abnormality such as left bundle branch block, atrioventricular (AV) block (2nd degree or higher), Wolff-Parkinson-White syndrome, atrial fibrillation, and atrial flutter. A long-standing right bundle branch block is permitted. 12. Participants cannot take investigational product with biologic agents (such as mAbs including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to signing the informed consent. 13. Past or intended use of over the counter or prescription medication, including herbal medications or cannabidiol (CBD)-based products within 14 days prior to administration of study intervention. 14. Recent infection or illness:
- Participants with any acute illness or infection requiring treatment within 28 days prior to Screening are excluded (but may be re-screened if appropriate).
- Participants with evidence of active infections, such as Coronavirus disease 2019 (COVID-19) or tuberculosis are excluded. 15. Participants who have received any live vaccines within 3 months prior to Screening or plan to receive such vaccines during the clinical study. 16. Positive drug screen at Screening, including tetrahydrocannabinol, indicating use of known recreational drugs or drugs of abuse. 17. An average weekly alcohol intake of >21 units per week for male participants and >14 units per week for female participants within 6 months prior to Screening. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits. 18. Any individual who is a current smoker or has a history of cigarette smoking of more than 5 pack years or regular use of tobacco- or nicotine-containing products within 6 months prior to Screening (including e-cigarettes or vaping). 19. Pregnancy and lactation:
- Participants of childbearing potential (POCBP) are excluded.
- Pregnant or breastfeeding females are excluded. 20. Participants who have donated 500 mL or more of blood or blood products within 12 weeks before administration of study intervention are excluded. 21. Concomitant conditions:
- Positive human immunodeficiency virus (HIV) antibody test. 22. Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for clinically established Gilbert's syndrome or asymptomatic gallstones). 23. Presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to first dose of study intervention. 24. Positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study intervention. 25. Positive hepatitis C RNA test result at Screening or within 3 months prior to first dose of study intervention. 26. History of severe reactions to IV or SC injections (e.g., anaphylaxis, vasovagal syncope).
Trial location(s)
No location data available.
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.